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Reactions to pain among subjects high and low in dental fear.

Differential pain tolerance might account for the diversity of reactions commonly seen in response to stressful medical and dental procedures. College students reporting themselves either highly fearful or nonfearful of dental work were compared in several aspects of their reactions to dental and nondental pain. The two groups did not differ in pain threshold or pain tolerance assessed during tooth pulp stimulation or during electrical stimulation of the forearm. High-dental fear subjects, however, retrospectively rated tooth shock (but not arm shock) more painful than low-fear subjects. High-fear subjects also showed significantly greater affective reactions assessed via the Anxiety Differential during both tolerance tests, with the group differences greater in magnitude during tooth shock than arm shock.

Animals↗

Pharmacological manipulations of anoxia-induced free fatty acid accumulation in the mouse brain.

The accumulation of free fatty acid (FFA) in the brain occurs within minutes of anoxia, induced by exposing mice to a 100% N2 atmosphere. The rate of FFA release is high within the first minute and continues to increase moderately hereafter. FFA is apparently accumulated at the highest concentration in the cerebral hemispheres. The release of FFA can be inhibited partly by CNS depressants like N6-cyclopentyladenosine, pentobarbital, ethanol, or 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3(2H)-one (THIP). Antiadrenergic compounds such as reserpine, clondine, or prazosine were also found to be active. The N2 anoxia was initially and temporarily associated with motor excitation termed fight and flight reaction. This behavior could be reduced by administration of N6-cyclopentyl-adenosine, pentobarbital, ethanol, reserpine, and prazosine, but not by THIP or clonidine. The glutamate antagonist MK-801 inhibited the fight and flight reaction, but did not affect the FFA accumulation. The data are consistent with the view that brain anoxia initially increases FFA by receptor-mediated polyphosphoinositide breakdown and that the alpha-1 adrenergic receptor is one of the receptors involved. The data also indicate that the fight and flight reaction is dissociated from the events that lead to FFA release, and may involve the stimulation of glutaminergic NMDA receptors.

Anesthetics↗

Pituitary and brain beta-endorphin in male and female rats: effects of shock and cues associated with shock.

The present experiment was designed to study whether or not prior exposure to inescapable shock is accompanied by sex-dependent changes in pituitary and central levels of immunoreactive beta-endorphin, which is proposed to play an important role in opioid analgesia induced by aversive stimulation. Further, the effects of brief reexposure (5 min) to the chamber where inescapable shock was experienced earlier, were established in both sexes. Elevated levels of beta-endorphin were found 24 hours after inescapable shock, in the anterior pituitary of males and in the midbrain periaqueductal gray of both males and females. Reexposure to the experimental chamber only affected beta-endorphin levels if shock had been experienced in this chamber. Reexposure after inescapable shock reduced beta-endorphin content of the arcuate nucleus of males and beta-endorphin content of the periaqueductal gray of males and females. The present results are related to previous findings of sensitization and conditioning of analgesic reactions. The sex differences found in the present experiment are discussed with respect to sex-dependent behavioral consequences of inescapable shock.

Animals↗

Ontogeny of defensive reactions in Norway rats.

Young rats of several ages were presented with stimuli (a caged domestic cat, a footshock, and a suddenly moving object) known to be aversive to adults and disruptive of behavior in mature animals. Twenty-day-old rats were relatively unaffected by these events, while rats aged 30 days and older tended to reduce their locomotion and freeze upon the presentation of these cues. These data are consistent with Bolles' hypothesis that shock-elicited responses are innate defensive reactions. We also suggest that the inefficient passive avoidance learning in juvenile rats may result from their deficit in shock-induced freezing.

Age Factors↗

[Training and extinction of passive avoidance in mice lacking monoamine oxidase A].

The passive avoidance learning and memory trace retention in mice lacking monoamine oxidase A (MAO A) and control C3H strain were analyzed. It is shown that mice of both strains were well the passive avoidance learners. A delay of the memory trace extinction was found in lacking MAO A mice as compared with control C3H strain. Mice with a genetic MAO A knockout showed decreased amounts of transitions, rearings, looking to a dark compartment and appearing from it. These findings seem to reflect more expressed fear reaction to a dangerous compartment and increased anxiety promoting longer retention of memory trace on a high level of retrieval.

Animals↗

Anatomical evidence that hypertension associated with the defence reaction in the cat is mediated by a direct projection from a restricted portion of the midbrain periaqueductal grey to the subretrofacial nucleus of the medulla.

Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections were made at sites within a restricted portion of the midbrain periaqueductal grey region (PAG) of the cat at which microinjection of the excitant amino acid, D.L-homocysteic acid, elicits the strongest form of a defence reaction, including a hypertensive response. Among the revealed projections, significant anterograde labelling was found in a discrete region of the rostral ventrolateral medulla, the subretrofacial nucleus (SRF). In the cat, the SRF contains pressor neurones which project to the spinal preganglionic sympathetic outflow. The labelling was most marked ipsilaterally, although substantial contralateral labelling was also observed. To verify that the projection to the SRF originated from the restricted 'defence region' of the PAG, WGA-HRP or rhodamine-labelled microspheres were injected into physiologically-identified sites in the SRF. In all experiments, labelled neurones were found in the same restricted region of the PAG at which DLH injection evokes hypertension and behavioural signs of the defence reaction. The results are consistent with the hypothesis that a discrete cell group within the PAG mediates both somatic and autonomic components of the defence reaction and that the characteristic hypertensive response is mediated by a direct pathway from these PAG cells to pressor neurones in the SRF.

Animals↗

Flight induced by microinjection of D-tubocurarine or alpha-bungarotoxin into medial hypothalamus or periaqueductal gray matter: cholinergic or GABAergic mediation?

Microinjections of various doses (50-300 ng) of the nicotinic antagonist D-tubocurarine (TUBO) into the rat's medial hypothalamus (MH) or dorsal periaqueductal gray (PAG) produced flight reactions characterized by jumps. Two different types of flight reactions were produced depending on whether the drug was injected into the MH or into the PAG. MH injections provoked an increase in both locomotor activity and rearing together with well-oriented jumps. PAG injections provoked either freezing reactions or running with explosive jumps, but no increase in rearing. In addition, the rat exhibited an asymmetry in responsiveness to tactile stimulation. These reactions also differed depending on whether the drug was injected into the dorsal or ventral PAG. Behavioral reactions similar to those produced by TUBO were also produced by microinjection of the GABA receptor antagonist bicuculline into the same brain sites. Among the 4 putative cholinergic antagonists tested under the same conditions only alpha-bungarotoxin produced effects that were qualitatively similar to those induced by D-tubocurarine or bicuculline. Gallamine and hemicholinium produced tremor when injected into sites located near the ventricular system at either the MH or the PAG level, while vocalizations were only produced by PAG injections. Hexamethonium produced no marked effect. The hypothesis that flight reactions induced by D-tubocurarine or alpha-bungarotoxin do not result from their antinicotinic action but rather from a direct effect on GABAergic transmission is discussed.

Acetylcholine↗

[The effect of the negative reinforcement system on the nonspecific nociceptive system of the thalamus in 41- to 60-day-old rabbits].

The work has been carried out in two steps. At the first one, in behavioural experiment, "punishment zones" were identified in animals, at the second step, in acute experiment, studies were made of the effect of stimulation of these zones on EP registered in CM-Pf in response to peripheral nociceptive stimulation. It was shown that stimulation of "punishment zones" inhibits the EP at currents lower critical level at which no avoidance reaction could be observed in behavioural experiment. Changes in the amplitude and duration of the EP depend on the aversive reaction to stimulation of these zones in the behavioural experiment. The sensitivity of CM-Pf to electrical stimulation of "punishment zones" remains constant with age.

Aging↗

Influence of ventral tegmental area (A10 region) on flight behaviour elicited by hypothalamic stimulation in the cat.

The influence of the ventral tegmental area (VTA) (dopaminergic A10 group neurons) on flight behaviour, induced by hypothalamic stimulation, was studied in the cat. Co-stimulation of hypothalamus and VTA (ipsi- or contralateral) induced an increase of the flight latency. Slow-motion analysis of flight behaviour showed that this increase was due to the augmentation of the fixation latency (FL) whereas the upright latency (UL) was not modified. Sulpiride injection (50 mg/kg i.p.) provoked the disappearance of VTA effect without affecting the basal behavioural sequence. The results show that DA A10 group neurons increase the attentive component of the flight reaction, suggesting a possible influence of the DA A10 system on the mechanisms modulating focused attention in the animal.

Anesthesia↗

Endocrine and behavioral traits in low-avoidance Sprague-Dawley rats.

In the present series of experiments, we have examined the endocrine profile of two stable colonies of Sprague-Dawley rats, here labeled Stock A, and Stock B, differing markedly in their ability to acquire a conditioned avoidance response. On separate occasions, the animals were subjected to five daily sessions (approximately 20 trials per 15 min session) of conditioned avoidance training, measurements of startle reactivity to an auditory stimulation and open-field spontaneous locomotor activity observations. The experiments were concluded by taking blood samples for later analysis of plasma glucose and plasma levels of the following hormones: insulin, gastrin, CCK, glucagon, somatostatin, oxytocin and corticosterone. The low-performing Stock B animals were characterized by [1] being more reactive to sensory stimulation: higher startle amplitude and shorter startle latency; [2] having higher plasma insulin and corticosterone levels, whereas plasma gastrin and oxytocin were significantly lowered and a strong tendency for a decrease also in plasma CCK. There were no differences in spontaneous locomotor activity between the two substrains. Taking total variability in avoidance performance into account, there was a statistically significant positive correlation between plasma oxytocin, as well as gastrin, levels and avoidance performance. The evidence obtained here, and in other laboratories, suggests that the Stock B animals display hormonal changes indicative of a submissive-defensive reaction pattern. Thus, the avoidance acquisition deficits displayed by the present Sprague-Dawley stocks A and B, are in all probability caused by emotional reactions when challenged with external stimuli requiring active responding.

Acoustic Stimulation↗

[The distribution in real time of the spike train activity in the cortical neurons of cats during learning].

Analysis of the dynamics of distribution of coincident impulses in pairs of neurons revealed modifications in the structure of neuronal interaction in the process of learning. In electrodefensive sound conditioning coincident paired impulses of the neurons in cat's motor cortex were timed to the moment of the conditioned stimulus presentation. In food-procuring time conditioning coincident impulses were concentrated around the moment of the reinforcement administration. The described temporal pattern of coincident impulse distribution is considered as a manifestation of a conditioned reaction at the level of neuronal interaction. This conclusion is confirmed by the finding that coincident impulses may be grouped within the period of expected conditioned reaction even in the absence of the defensive or food-procuring movement in well-trained cats.

Acoustic Stimulation↗

[The dynamics of latent inhibition in rats under the action of substance P].

The role of substance P in latent inhibition was studied in experiments on rats. Administration of neuropeptide during pre-exposition of conditioned stimulus and before conditioning disturbed all signs of latent inhibition: level of reproduction, retention and resistance to amnestic action of conditioned reaction in the task of passive avoidance. Single administration of haloperidol before learning prevented the disturbance. Significance of hyperfunction of substance P in selective attention and pathogenesis of schizophrenia is discussed.

Animals↗

[The neurochemical basis of recurrent inhibition in the reflex arch of the defensive reaction].

Mechanisms of habituation in the network of identified neurones were investigated in isolated preparation of central nervous system in the snail Helix. It has been found that intracellularly induced spike discharge in premotor command neurones decreases synaptic responses to repeated nerve stimulation in all recorded command neurones. Application of the neuropeptide FMRFamide elicits similar changes in the network. Taking into account that the investigated command neurones contain FMRFamide, as was shown immunochemically, it is possible to assume the existence of recurrent inhibition in the network underlying avoidance reactions. This recurrent inhibition causes habituation of the network output in the cases when the repeated stimuli do not evoke sensitization via activation of serotonergic cells.

Action Potentials↗

[The characteristics of the participation of the neostriatal cholinergic system in regulating different forms of defensive behavior].

The effects of microinjections of the cholinergic agonist (carbacholine) into the dorsal part of the neostriatum on discrimination processing of sensory signals were studied in chronic experiments in dogs (instrumental defensive reflex connected with maintenance of flexion posture) and in rats (active avoidance learning in T-maze). It was found that an improvement of discrimination process after carbacholine injections was manifested as an increase in the number of correct responses during acquisition of discriminative avoidance reflex in T-maze (rats) and during differentiation of sound signals in instrumental defensive reaction (dogs). The efficacy of this influences was suggested to be depend on the level of animal learning. We did not shown an improvement of the responses in two cases: 1. When before the microinjections the responses on the defensive and on the discriminative signals did not distinguish; 2. Under total differentiation of signals (e. g. under total learning). In both cases the neostriatum seems to be not involved in behavioral reaction what could be accompanied by low neuronal activity during the these signals action.

Acetylcholine↗

Comparison of peripheral blood flow patterns associated with the defense reaction and the vigilance reaction in rabbits.

The present study compared the skeletal muscle and visceral blood flow patterns elicited by electrical stimulation of the hypothalamic defense area (HDA) and the hypothalamic vigilance area (HVA) of the rabbit. Electrical stimulation of the HDA evoked a pressor response, tachycardia, hyperventilation, an increase in blood flow to the skeletal muscles and decreased blood flow to visceral organs. Stimulation of the HVA yielded a pressor response, bradycardia, inspiratory apnea and decreased blood flow to both the skeletal muscles and the viscera. Intravenous injections of atropine methyl nitrate significantly reduced the HVA-elicited bradycardia and the HDA-elicited increase in blood flow to the skeletal muscles, thereby providing evidence that the bradycardia was mediated by vagal efferents and that the rabbit has an atropine-sensitive cholinergic vasodilation system. The decrease of blood flow to the visceral organs associated with the defense reaction and vigilance reaction was reversed by intravenous injections of the alpha-1 receptor blocker prazosin.

Animals↗

Prior electrical stimulation of dorsal periaqueductal grey matter or deep layers of the superior colliculus sensitizes rats to anxiety-like behaviors in the elevated T-maze test.

Electrical stimulation of the dorsal periaqueductal grey matter (DPAG) and deep layers of the superior colliculus (DLSC) of the rat elicits anxiety-like reactions such as freezing and flight. The temporal course of the effects of the aversive electrical stimulation of the DPAG (5, 15 and 30 min afterward) and DLSC (5, 10 and 15 min afterward) on the defensive response of rats exposed to elevated T-maze were determined. The elevated T-maze generates two defensive behaviors, inhibitory avoidance and one-way escape, which have been related, respectively, to generalized anxiety and panic disorders. Prior electrical stimulation of the DPAG (15 min) and DLSC (5 min) enhanced inhibitory avoidance when compared to no-operated and sham animals, although not affecting escape. Therefore, stimulation of the DPAG and DLSC causes a heightened responsivity to anxiogenic stimulus, but not to panicogenic stimulus, inherent to elevated T-maze. These findings support the participation of the DPAG and DLSC in the elaboration of adaptive responses to stressful situations. Besides, the data supports the view that prior electrical stimulation of DPAG and DLSC is selective in sensitizing rats to anxiety-like behaviors, but not to panic-like behaviors in the elevated T-maze test.

Animals↗

Acquisition and extinction of a conditioned passive avoidance reflex in mice with genetic knockout of monoamine oxidase A.

We report here the results obtained from comparative analysis of learning and the dynamics of extinction of a conditioned passive avoidance response in mice with genetic knockout of monoamine oxidase A (MAO A) and the progenitor line C3H. Mice of both lines acquired the conditioned passive avoidance reaction efficiently. Mice with genetic knockout of MAO A were characterized by prolonged retention of reproduction of the memory trace, as compared with rapid extinction in C3H mice. Smaller numbers of transfers, and vertical rearings on days 7-13 and the numbers of glances into and rom the dark sector on days 11-13 of extinction in MAO A-knockout mice appear to reflect their more marked fear reactions when confronted with the "dangerous" sector, along with increased anxiety, these facilitating longer-lasting retention of the memory trace.

Analysis of Variance↗